Effect of Pneumococcal Conjugate Vaccines on Pneumococcal Meningitis, England and Wales, July 1, 2000–June 30, 2016

Godwin Oligbu; Sarah Collins; Abdelmajid Djennad; Carmen L. Sheppard; Norman K. Fry; Nick J. Andrews; Ray Borrow; Mary E. Ramsay; Shamez N. Ladhani


Emerging Infectious Diseases. 2019;25(9):1708-1718. 

In This Article

Abstract and Introduction


We describe the effects of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines on pneumococcal meningitis in England and Wales during July 1, 2000–June 30, 2016. Overall, 84,473 laboratory-confirmed invasive pneumococcal disease cases, including 4,160 (4.9%) cases with meningitis, occurred. PCV7 implementation in 2006 did not lower overall pneumococcal meningitis incidence because of replacement with non–PCV7-type meningitis incidence. Replacement with PCV13 in 2010, however, led to a 48% reduction in pneumococcal meningitis incidence by 2015–16. The overall case-fatality rate was 17.5%: 10.7% among patients <5 years of age, 17.3% among patients 5–64 years of age, and 31.9% among patients ≥65 years of age. Serotype 8 was associated with increased odds of death (adjusted odds ratio 2.9, 95% CI 1.8–4.7). In England and Wales, an effect on pneumococcal meningitis was observed only after PCV13 implementation. Further studies are needed to assess pneumococcal meningitis caused by the replacing serotypes.


Streptococcus pneumoniae is a major cause of bacterial meningitis across all age groups in the United Kingdom and worldwide;[1,2] the case-fatality rate (CFR) ranges from 10% to 40%.[2–4] Survivors of pneumococcal meningitis are more likely than survivors of other types of bacterial meningitis to have neurologic and other serious long-term sequelae;[5,6] a meta-analysis indicated that 32% of pneumococcal meningitis patients experienced sequelae.[7] The pathophysiologic mechanisms leading to neurologic damage in patients with bacterial meningitis are complex and multifaceted, involving the secretion of potent bacterial toxins and excessive host immune responses against the invading pneumococci in the cerebrospinal fluid.[8,9]

Before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), ≈500 confirmed pneumococcal meningitis cases occurred annually in England and Wales.[2] The serotypes covered by PCV7 were responsible for 57% of all pneumococcal meningitis cases and 72% of cases in children <2 years of age; the CFR increased with age, from 5% in children to 30% in older adults.[10]

In September 2006, the United Kingdom introduced PCV7 into the childhood immunization program; children were scheduled to receive the vaccine at 2, 4, and 12 months of age, and a 12-month catch-up program was established for children <2 years of age.[11] The program was associated with a rapid decline in invasive pneumococcal disease (IPD) caused by PCV7 serotypes, and although some increase in IPD caused by non-PCV7 serotypes was observed, IPD decreased overall by 36% compared with pre-PCV7 levels through direct and indirect protection.[12] During the first 4 years of the program, a 34% reduction in pneumococcal meningitis incidence was observed in children <5 years of age.[13] However, this reduction was almost entirely offset by an increase in meningitis cases caused by non-PCV7 serotypes in older children and adults. After PCV7 introduction, pneumococcal meningitis was mainly caused by serotypes 1, 3, 7F, 19A, 22F, and 33F.[14]

In April 2010, PCV7 was replaced with the 13-valent vaccine (PCV13), which led to a 32% reduction in overall IPD incidence compared with pre-PCV7 levels and a 56% reduction compared with pre-PCV13 levels.[14] The effect of PCV13 on pneumococcal meningitis has not been assessed in the United Kingdom. Reports of the effects of PCV7 and PCV13 on pneumococcal meningitis in other countries with established pneumococcal immunization programs have been variable; in some countries, significant reductions were reported after PCV7 introduction, and in other countries, no change or a decline was reported only after PCV13 introduction.[15–20] Here, we describe the epidemiology of pneumococcal meningitis in England and Wales over a 16-year period encompassing the introduction of PCV7 and PCV13 into the national immunization program.